New Advances in Small Molecules Targeted at Viral Capsid-Genome Binding.

Publication date: Jul 20, 2025

The capsid protein plays a crucial role in the viral life cycle. By interacting with the viral genome, it facilitates the assembly of the nucleocapsid, ultimately leading to the formation of the viral particle. Therefore, interfering with or disrupting the interaction between the capsid protein and viral genome can effectively inhibit viral replication and infection. This review focuses on elucidating the binding mechanisms between the capsid protein and the viral genome, as well as their potential applications as therapeutic targets. In particular, it summarizes the research progress on small-molecule drugs targeting the capsid-genome binding sites of dengue virus, HBV, and SARS-CoV-2. Notably, this review provides a detailed discussion on the mechanisms by which these small-molecule inhibitors interfere with the capsid-genome interaction, aiming to offer inspiration for the future development of novel antiviral drugs targeting the capsid-genome binding.

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Concepts Keywords
Crucial Animals
Dengue Antiviral Agents
Drugs Antiviral Agents
Genome antiviral strategy
Viral Binding Sites
Capsid
capsid protein (Cp)
Capsid Proteins
Capsid Proteins
capsid–genome binding
COVID-19 Drug Treatment
Dengue Virus
Genome, Viral
Hepatitis B virus
Humans
Protein Binding
SARS-CoV-2
small molecule
Small Molecule Libraries
Small Molecule Libraries
viral inhibitor
Virus Replication

Semantics

Type Source Name
disease IDO role
pathway KEGG Viral life cycle
pathway KEGG Viral replication
disease MESH infection
disease MESH viral infections
disease IDO protein
disease IDO process
disease MESH hepatitis
disease IDO assay
drug DRUGBANK Phosphate ion
drug DRUGBANK L-Tryptophan
disease IDO replication
disease MESH viral hemorrhagic fever
disease MESH Defects
disease IDO site
disease MESH dengue
drug DRUGBANK Masoprocol
drug DRUGBANK Safinamide
drug DRUGBANK L-Arginine
drug DRUGBANK L-Lysine
drug DRUGBANK L-Cysteine
disease IDO nucleic acid
disease IDO cell
drug DRUGBANK Serine
drug DRUGBANK L-Threonine
disease MESH chronic hepatitis
drug DRUGBANK Natural alpha interferon
drug DRUGBANK Polyethylene glycol
drug DRUGBANK Trestolone
drug DRUGBANK Phenylpropanolamine
drug DRUGBANK Oxygen
drug DRUGBANK Urea
drug DRUGBANK Nitrogen
disease MESH COVID 19 pandemic
drug DRUGBANK ATP
drug DRUGBANK Thiocolchicoside
drug DRUGBANK Amber
disease IDO host
disease IDO bacteria
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH Venezuelan Equine Encephalitis
disease MESH neonatal sepsis
drug DRUGBANK Ribostamycin
drug DRUGBANK Guanosine
drug DRUGBANK Troleandomycin
drug DRUGBANK Efavirenz
drug DRUGBANK Diethylstilbestrol
drug DRUGBANK Carboxyamidotriazole

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